Coverage and uptake of antivirals and neutralising monoclonal antibodies for the treatment of non-hospitalised patients with COVID-19

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Overview

This OpenSAFELY report was rapidly developed to support monitoring the ongoing roll-out of antivirals and neutralising monoclonal antibodies (nMABs) for the treatment of COVID-19, based on the population of 23.4m people registered with practices that use TPP SystmOne software. This report will be updated approximately weekly as new data arrives.

The code and data for this report can be found at the OpenSAFELY antibody-and-antiviral-deployment repository. The accompanying manuscript will be available shortly on MedRXiV (link to follow) and submitted for peer review.

Contents

• Introduction
• Results
  • Coverage of COVID-19 treatment
  • High risk patient cohorts
  • Key demographic and clinical characteristics of treated patients
  • Consistency with guidance
  • Time to treatment
• Methods

Introduction

While vaccines remain the best strategy to prevent COVID-19, recent evidence suggests neutralising monoclonal antibodies (nMABs) or antivirals could potentially benefit certain vulnerable populations before or after exposure to SARS-CoV-2, such as the unvaccinated or recently vaccinated high-risk patients. On 16th December 2021, new COVID-19 Medicine Delivery Units (CMDUs) were launched across England, offering antiviral medicines and neutralising monoclonal antibodies (nMABs) as treatment to patients with COVID-19 at high risk of severe outcomes in outpatient clinics or their own home.

With the recent roll-out of nMABs and antivirals, there is an urgent need assess the coverage of these new treatments amongst these patients, such as factors of relevance in determining nMAB and antiviral treatment and the impact of nMAB and antiviral treatment in the community and hospital settings.

Using the OpenSAFELY platform we have developed and delivered a rapid, near real-time data-monitoring framework for the roll-out of antivirals and nMABs in England that can deliver detailed coverage reports in fine-grained clinical and demographic risk groups, using publicly auditable methods, using linked but pseudonymised patient-level NHS data in a highly secure Trusted Research Environment.

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods can be found at the end of the this report.

Results

Overall coverage of COVID-19 treatment

Between 11-Dec-2021 and 23-Feb-2022, a total of 50,730 non-hospitalised patients registered at a TPP practice in England were identified as potentially being eligible for receiving an antiviral or nMAB for treating COVID-19. Of the 50,730 potentially eligible patients, (15%) were classified into more than one high risk cohort (high risk cohort count range 1 - 6). The number of patients potentially eligible in each high risk cohort is described in Figure 1 and Table 1 below.

Of the 50,730 potentially eligible patients, 6,460 (13%) received treatment from a CMDU (Table 1, Figure 2);

• Paxlovid: 110;
• Sotrovimab: 3,610;
• Remdesivir: 0;
• Molnupiravir: 2,680;
• Casirivimab: 50.

Figure 1 Cumulative total of potentially eligible patients for receiving an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohort. Patients are considered eligible on the date of their positive SARS-CoV-2 test. Note, patients can appear in more than one high risk group, and the overall number in each group is likely to be an overestimation due to including SARS-CoV-2 infection confirmed by either lateral flow or PCR test (where only PCR-confirmed infections should have been treated according to guidance in effect prior to 10th February 2022), and potentially including non-symptomatic patients.

Figure 2 Cumulative total of patients who received an antiviral or nMAB for treating COVID-19 since 16th December 2021, stratified by (a) treatment type and (b) high risk cohorts. Shorter lines for Paxlovid and casirivimab reflect availability and guidance. Note, treated patients can appear in more than one high risk group.

(b)

Table 1 Count and proportion of potentially eligible patients in OpenSAFELY-TPP who have received treatment for COVID-19 between 16th December 2021 23rd February 2022, broken down by high risk cohort and treatment type. Patient counts >5 are rounded to the nearest 10; as a result percentages may not add up to 100%.

		Treated
	Eligible	All		Paxlovid		Sotrovimab		Remdesivir		Molnupiravir		Casirivimab
High risk cohort	Count	Count	%	Count	%	Count	%	Count	%	Count	%	Count	%
All	50730	6420	13 (12-13)	80	1 (1-2)	3600	56 (55-57)	<5	–	2680	42 (41-43)	50	1 (1-1)
Immune-mediated inflammatory disorders	20390	3030	15 (14-15)	30	1 (1-1)	1720	57 (55-59)	<5	–	1250	41 (40-43)	20	1 (0-1)
Primary immune deficiencies	9940	1190	12 (11-13)	20	2 (1-2)	620	52 (49-55)	<5	–	540	45 (43-48)	10	1 (0-1)
Solid cancer	8370	950	11 (11-12)	10	1 (0-2)	550	58 (55-61)	<5	–	380	40 (37-43)	10	1 (0-2)
Rare neurological conditions	5680	920	16 (15-17)	20	2 (1-3)	480	52 (49-55)	<5	–	420	46 (42-49)	10	1 (0-2)
Haematological diseases and stem cell transplant recipients	4530	930	21 (19-22)	10	1 (0-2)	520	56 (53-59)	<5	–	390	42 (39-45)	10	1 (0-2)
Solid organ transplant recipients	3490	860	25 (23-26)	<5	–	560	65 (62-68)	<5	–	290	34 (31-37)	10	1 (0-2)
Renal disease	3160	800	25 (24-27)	<5	–	540	68 (64-71)	<5	–	260	32 (29-36)	10	1 (0-2)
Liver disease	3130	320	10 (9-11)	<5	–	170	53 (48-59)	<5	–	140	44 (38-49)	<5	–
Down’s syndrome	1090	150	14 (12-16)	<5	–	50	33 (26-41)	<5	–	100	67 (59-74)	<5	–
Immunosuppression due to HIV or AIDS	330	190	58 (52-63)	<5	–	70	37 (30-44)	<5	–	120	63 (56-70)	<5	–
* High risk cohorts are arranged in descending order, according to number of potentially eligible patients
† All percentages (%) are caluclated with 95% confidence intervals

High risk patient cohorts

The proportion of potentially eligible patients receiving treatment varied over time and by high risk cohort (Figure 3).

Figure 3 Weekly proportion of eligible patients receiving an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by high risk cohort

Key demographic and clinical characteristics of treated patients

Table 2 shows the count and proportion of potentially eligible patients who received treatment for COVID-19 by 23-Feb-2022, broken down by demographic and clinical categories and by treatment type. The proportion treated varied by ethnicity, NHS Regions and by rurality. There was also lower coverage among care home residents, those with dementia, those with sickle cell disease, unvaccinated patients and in the most socioeconomically deprived areas. Patients who were housebound, or who had a severe mental illness also had a slightly reduced chance of being treated.

Table 2 Count and proportion of potentially eligible patients in OpenSAFELY-TPP who have received treatment for COVID-19 between 11th December 2021 and 23rd February 2022, broken down by demographic and clinical categories and by treatment type. Patient counts >5 are rounded to the nearest 10; as a result percentages may not add up to 100%.

			Treated
		Eligible	All		Paxlovid		Sotrovimab		Remdesivir		Molnupiravir
Group	Variable	Count	Count	%	Count	%	Count	%	Count	%	Count	%
Age band	12-29	5050	550	11 (10-12)	10	2 (1-3)	300	55 (50-59)	<5	–	230	42 (38-46)
Age band	30-39	6470	990	15 (14-16)	10	1 (0-2)	570	58 (54-61)	<5	–	390	39 (36-42)
Age band	40-49	8390	1320	16 (15-17)	20	2 (1-2)	750	57 (54-59)	<5	–	530	40 (38-43)
Age band	50-59	10050	1450	14 (14-15)	40	3 (2-4)	820	57 (54-59)	<5	–	580	40 (37-43)
Age band	60-69	8740	1130	13 (12-14)	20	2 (1-3)	640	57 (54-60)	<5	–	460	41 (38-44)
Age band	70-79	7330	760	10 (10-11)	10	1 (1-2)	410	54 (50-57)	<5	–	340	45 (41-48)
Age band	80+	4700	270	6 (5-6)	<5	–	110	41 (35-47)	<5	–	150	56 (50-61)
Sex	Female	28640	3810	13 (13-14)	70	2 (1-2)	2170	57 (55-59)	<5	–	1550	41 (39-42)
Sex	Male	22090	2650	12 (12-12)	40	2 (1-2)	1440	54 (52-56)	<5	–	1130	43 (41-45)
Sex	Unknown	<5	<5	–	<5	–	<5	–	<5	–	<5	–
Ethnicity	White	40570	5480	14 (13-14)	100	2 (1-2)	3090	56 (55-58)	<5	–	2240	41 (40-42)
Ethnicity	Asian or Asian British	2540	330	13 (12-14)	<5	–	210	64 (58-69)	<5	–	120	36 (31-42)
Ethnicity	Black or Black British	2030	190	9 (8-11)	<5	–	100	53 (46-60)	<5	–	80	42 (35-49)
Ethnicity	Mixed	670	80	12 (9-14)	<5	–	40	50 (39-61)	<5	–	40	50 (39-61)
Ethnicity	Other ethnic groups	830	90	11 (9-13)	<5	–	40	44 (34-55)	<5	–	50	56 (45-66)
Ethnicity	Unknown	4090	290	7 (6-8)	10	3 (1-6)	130	45 (39-51)	<5	–	150	52 (46-57)
IMD	1 most deprived	10310	920	9 (8-9)	20	2 (1-3)	530	58 (54-61)	<5	–	370	40 (37-43)
IMD	2	10000	1180	12 (11-12)	20	2 (1-2)	650	55 (52-58)	<5	–	500	42 (40-45)
IMD	3	10340	1450	14 (13-15)	20	1 (1-2)	800	55 (53-58)	<5	–	610	42 (40-45)
IMD	4	9720	1350	14 (13-15)	20	1 (1-2)	770	57 (54-60)	<5	–	550	41 (38-43)
IMD	5 least deprived	8970	1380	15 (15-16)	30	2 (1-3)	760	55 (52-58)	<5	–	580	42 (39-45)
IMD	Unknown	1400	180	13 (11-15)	<5	–	100	56 (48-63)	<5	–	80	44 (37-52)
Rurality	Urban - conurbation	13660	1370	10 (10-11)	20	1 (1-2)	770	56 (54-59)	<5	–	580	42 (40-45)
Rurality	Urban - city and town	26040	3470	13 (13-14)	70	2 (2-2)	1840	53 (51-55)	<5	–	1520	44 (42-45)
Rurality	Rural - town and fringe	5900	850	14 (14-15)	10	1 (0-2)	520	61 (58-64)	<5	–	310	36 (33-40)
Rurality	Rural - village and dispersed	3790	590	16 (14-17)	10	2 (1-3)	380	64 (61-68)	<5	–	200	34 (30-38)
Rurality	Unknown	1350	180	13 (12-15)	<5	–	100	56 (48-63)	<5	–	80	44 (37-52)
Region	East Midlands	9050	1060	12 (11-12)	20	2 (1-3)	740	70 (67-73)	<5	–	280	26 (24-29)
Region	East of England	12000	2040	17 (16-18)	10	0 (0-1)	1110	54 (52-57)	<5	–	890	44 (41-46)
Region	London	3210	420	13 (12-14)	10	2 (1-4)	160	38 (33-43)	<5	–	250	60 (55-64)
Region	North East	2730	320	12 (11-13)	<5	–	240	75 (70-80)	<5	–	80	25 (20-30)
Region	North West	5340	610	11 (11-12)	20	3 (2-5)	300	49 (45-53)	<5	–	290	48 (44-52)
Region	South East	3240	430	13 (12-14)	10	2 (1-4)	240	56 (51-61)	<5	–	180	42 (37-47)
Region	South West	5880	940	16 (15-17)	30	3 (2-4)	440	47 (44-50)	<5	–	460	49 (46-52)
Region	West Midlands	2080	250	12 (11-13)	<5	–	200	80 (75-85)	<5	–	50	20 (15-25)
Region	Yorkshire and the Humber	7140	400	6 (5-6)	10	2 (1-4)	180	45 (40-50)	<5	–	210	52 (48-57)
Region	Unknown	70	10	14 (6-22)	<5	–	0	0 (0-0)	<5	–	<5	–
Autism	Autism	300	40	13 (9-17)	<5	–	20	50 (35-65)	<5	–	30	75 (62-88)
Care home	Care home	1700	60	4 (3-4)	<5	–	10	17 (7-26)	<5	–	50	83 (74-93)
Dementia	Dementia	1230	50	4 (3-5)	<5	–	10	20 (9-31)	<5	–	30	60 (46-74)
Learning disability	Learning disability	1310	170	13 (11-15)	0	0 (0-0)	60	35 (28-42)	<5	–	100	59 (51-66)
Serious mental illness	Serious mental illness	700	70	10 (8-12)	<5	–	30	43 (31-54)	<5	–	30	43 (31-54)
Housebound	Housebound	1830	180	10 (8-11)	<5	–	90	50 (43-57)	<5	–	80	44 (37-52)
CEV	CEV	26850	4570	17 (17-17)	70	2 (1-2)	2600	57 (55-58)	<5	–	1860	41 (39-42)
Sickle cell disease	Sickle cell disease	750	50	7 (5-8)	<5	–	20	40 (26-54)	<5	–	20	40 (26-54)
Vaccination status	Un-vaccinated (declined)	790	30	4 (2-5)	<5	–	20	67 (50-84)	<5	–	10	33 (16-50)
Vaccination status	Un-vaccinated	2310	120	5 (4-6)	<5	–	60	50 (41-59)	<5	–	60	50 (41-59)
Vaccination status	One vaccination	1580	130	8 (7-10)	<5	–	70	54 (45-62)	<5	–	50	38 (30-47)
Vaccination status	Two vaccinations	7330	520	7 (7-8)	10	2 (1-3)	280	54 (50-58)	<5	–	220	42 (38-47)
Vaccination status	Three or more vaccinations	38720	5660	15 (14-15)	100	2 (1-2)	3190	56 (55-58)	<5	–	2340	41 (40-43)
* Due to not being used after December 2021, Casirivimab had been omitted from this table
* All percentages (%) are caluclated with 95% confidence intervals

Consistency with guidance

Of the 6,460 patients who received treatment for COVID-19 between 11-Dec-2021 and 23-Feb-2022, 1,255 patients were missing records needed to confirm eligibility; 2% did not have evidence of a positive SARS-CoV-2 test, 16% did not have a high risk cohort identified from their GP records alone, and 1% were discharged from hospital within 30 days prior to their positive test or treatment date, where COVID-19 was the primary diagnosis. There were also a small number of other potential inconsistencies with guidance for patients who received treatment, such as having a potential contraindication to the treatment given (Figure 3).

Figure 3 Breakdown of possible inconsistencies with guidance on eligibility/exclusion criteria in treated COVID-19 patients. Treatment eligibility window for Paxlovid, sotrovimab and molnupiravir was 5 days from positive SARS-CoV-2 test (used as a proxy for symptom onset date) and 7 days for remdesivir.

Time to treatment

Overall, of the 6,460 patients who received treatment, 94% did so within the respective treatment-specific eligibility window as estimated from test date (as symptom date is not consistently available) (Figure 4).

Figure 4 Time (number of days) between positive SARS-CoV-2 test and treatment for COVID-19, broken down by (a) treatment type and (b) high risk cohort.

Methods

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods are given below.

Data sources

All data were analysed securely through OpenSAFELY-TPP https://opensafely.org which contains the full pseudonymised primary care records for all patients currently registered with general practices using TPP SystmOne software (approximately 23.4 million, 40% of the English population). Data were linked with accident and emergency (A&E) attendance and in-patient records from NHS Digital; national coronavirus testing records from the Second Generation Surveillance System (SGSS); and the “COVID-19 therapeutics dataset”, a patient-level dataset on antiviral and nMAB treatments from NHS England, derived from software used to notify NHS England of COVID-19 treatments.

Study population

Base population

• Patients with either a positive SARS-CoV-2 test on or after 11th December 2021 (this is the earliest date that a patient could have tested positive and still been eligible for receiving treatment when they became available from CMDUs from 16th December 2021) or with a treatment record on or after 16th December 2021, who were also registered at the time of their test/treatment.
• Patients aged under 12 or with an unknown date of birth were excluded.

Eligible patients

Where possible eligibility criteria were applied as per the Interim Clinical Commissioning Policy for non-hospitalised COVID-19 patients (NHSE, 28/01/2022) this included:

• SARS-CoV-2 infection confirmed by a PCR or lateral flow test
• being a member of a high risk cohort (determined by applying the detailed codelists and logic from NHS Digital as far as possible)

There were two main differences to the official criteria in our implementation. Firstly, prior to 10th February 2022, infection should have been confirmed by a PCR test, however this was then relaxed to include lateral flow tests. We were not able to always distinguish between lateral flow and PCR tests in all test records, and therefore included all positive SARS-CoV-2 test results. Secondly, having symptomatic COVID-19 was also an eligibility criteria: however due to difficulties in determining symptom status (i.e. it was only possible to determine whether a patient’s positive test had a “symptomatic” flag at the time of the test, but not whether symptoms developed later) we did not implement this requirement in our analysis; however we do address this in a separate sensitivity analysis, where we restricted the potentially eligible population to only those with a “symptomatic” flag associated with their positive SARS-CoV-2 test to determine its use as an indicator of being potentially asymptomatic.We also included patients in the eligible population if they were in the Treated cohort below.

Treated patients

• Treatments and the date they were given were identified in the COVID-19 therapeutics dataset, restricted to those treated in the community (“non_hospitalised”)
• Patients issued more than one treatment within two weeks of one another, or with an implausible treatment date (e.g. far in the future) were excluded

Key demographic and clinical characteristics

We classified treated patients by age group, sex, NHS region of their general practice and other key demographics including ethnicity and the level of deprivation. Deprivation was measured by Index of Multiple Deprivation (IMD), in quintiles, derived from the patient’s postcode at lower super output area level for a high degree of precision. Ethnicity was ascertained using 270 clinical codes grouped into broad categories White, Black or Black British, Asian or Asian British, Mixed, Other, and Unknown. Individuals with missing sex, ethnicity, IMD or region were included as “Unknown”. Treated patients were described according to whether they were in other groups of interest who are sometimes subject to variation in care, including autism, dementia, learning disability, serious mental illness, care home residents, and housebound. In addition we classified treated patients by their COVID-19 vaccination status (unvaccinated, unvaccinated with a record of declining vaccination, one vaccination, two vaccinations, or three or more).

Consistency with guidance

For patients who received treatment but who were not otherwise identified as potentially being eligible for treatment, we report which eligibility or exclusion criteria were not met according to the data available (i.e. no positive SARS-CoV-2 test result, or not identified as part of a high risk group). Where possible within available data, we also report other potential inconsistencies with guidance for patients who received treatment, such as where the high risk cohort identified within their records did not match the high risk cohort associated with their treatment.

We also assess consistency with treatment-specific criteria, such as patients having a recorded contraindication to the specific treatment given (e.g. adolescents treated with sotrovimab/remdesivir with weight under 40kg, Table S2), or patients treated outside the prescribed timescale, 5-7 days from symptom onset, depending on the treatment. As symptom onset date was not available, here we used positive SARS-CoV-2 test as a proxy to estimate the extent to which patients may or may not have been treated outside the guidance time window.

Descriptive statistics

We generated charts showing the cumulative number of potentially eligible and treated patients per week, stratified by high risk group, and also stratified by treatment type for treated patients. We used simple descriptive statistics to summarise the counts and proportions of potentially eligible patients treated, stratified by treatment type and either high risk cohort or clinical and demographic groups, and to describe potential inconsistencies with guidelines. Charts and results not presented in this manuscript are available online for inspection in the associated Github antibody-and-antiviral-deployment repository. Patient counts of 0-5 are shown as “<5” with remaining counts rounded to the nearest 10 to protect against small number differences in our routinely updating data. All percentages (%) are calculated with 95% confidence intervals (CI).

Codelists

Detailed information on compilation and sources for every individual codelist are available at https://www.opencodelists.org/.